The invention relates to effervescent mixtures containing at least one acidic, insoluble or slightly soluble pharmaceutical active ingredient in the form of its soluble alkali metal salt or lysinate. Such pharmaceutical active ingredients are, for example, organic derivatives of acetic acid or propionic acid, for example ibuprofen, naproxen, diclofenac, butabarbital, phenobarbital, cefazolin, diatrizoate, ethacrynate, flurbiprofen, sulfacetamide or hetacillin.
The acidic active ingredients cannot, as a rule, be obtained in finely disperse or colloidal form and are therefore preferably administered as their potassium salts (for example hetacillin) or lysinates (for example ibuprofen) or as their sodium salts (including ibuprofen and most of the other active ingredients mentioned above) in solution.
In contrast to the pure acids, the alkali metal salts of such active ingredients are generally freely water-soluble but often have a bitter taste and are precipitated from acidic solutions frequently in lumpy form and/or with foam formation; the same occurs in the case of solid dosage forms as a result of the gastric acid. These active ingredients therefore easily lead to irritation of the stomach walls.
To avoid these disadvantages, EP-A1-369 228 has already proposed granulating 100 parts by weight of a water-soluble ibuprofen salt with 200 to 1000 parts by weight of vehicle, 30 to 80 parts by weight of stabilizer (for example polyvinylpyrrolidone, "PVP") and 10 to 100 parts by weight of an alkali metal carbonate, and mixing the resulting granules with 100 to 400 parts by weight of the acid component. The aim here is to obtain the sodium salt in solution after dissolution of the effervescent tablet. This is achieved, inter alia, by virtue of the fact that the pH is in any case always above 6 in the case of the chosen composition. However, such a solution has an unpleasant taste, for example diclofenac sodium even has a bitter taste. In addition, very large amounts of PVP are required to prevent precipitation of the active ingredient as acid during effervescence.